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Details

Stereochemistry ACHIRAL
Molecular Formula C21H20N4O3
Molecular Weight 376.4085
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENTINOSTAT

SMILES

NC1=CC=CC=C1NC(=O)C2=CC=C(CNC(=O)OCC3=CN=CC=C3)C=C2

InChI

InChIKey=INVTYAOGFAGBOE-UHFFFAOYSA-N
InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26)

HIDE SMILES / InChI

Molecular Formula C21H20N4O3
Molecular Weight 376.4085
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17383217 https://www.ncbi.nlm.nih.gov/pubmed/21888556 https://www.ncbi.nlm.nih.gov/pubmed/12975486

Entinostat (MS-275) is an orally active, highly selective, small-molecule histone deacetylase inhibitor (HDACi) derived from benzamide. Entinostat preferentially inhibited HDAC1 versus HDAC3 and had no inhibitory activity toward HDAC8. The time to maximum plasma concentration (tmax) of entinostat ranged from 0.5 to 60h (median of 2h). Elimination of the drug was bi-exponential, with a terminal half-life of 30-80h. Entinostat is a well-tolerated that demonstrates promising therapeutic potential in both solid and hematologic malignancies. Its efficacy does not appear directly dose-related, and as such, more relevant biomarkers are needed to adequately assess its activity.

CNS Activity

Curator's Comment: Entinostat (MS-275) is a potent brain region-selective HDAC inhibitor in mice. https://www.ncbi.nlm.nih.gov/pubmed/16432198 Other study demostartes poor Entinostat (MS-275) brain penetration in non-human primates and rodents. https://www.ncbi.nlm.nih.gov/pubmed/20657706 No human data reported to date.

Originator

Curator's Comment: # Nihon Schering; Pfizer; University of Tokyo

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.3 µM [IC50]
8.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors.
2002 Nov 1
The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1.
2003 Jul 1
Induction of fetal hemoglobin expression by the histone deacetylase inhibitor apicidin.
2003 Mar 1
Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry.
2005 Autumn
Histone deacetylase inhibitors promote osteoblast maturation.
2005 Dec
Peak shape improvement of basic analytes in capillary liquid chromatography.
2005 Feb
[A new target of cancer therapy: advances in the study of histone deacetylase].
2005 Jul
Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-kappaB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation.
2005 Jul
Histone deacetylase inhibitors and cancer: from cell biology to the clinic.
2005 Mar
Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase inhibitor MS-275 in human renal cell carcinoma.
2005 May 1
Targeting epigenetic changes in acute myeloid leukemia.
2005 Nov
Early clinical data and potential clinical utility of novel histone deacetylase inhibitors in prostate cancer.
2005 Sep
Interspecies differences in plasma protein binding of MS-275, a novel histone deacetylase inhibitor.
2006 Feb
Curcumin is an inhibitor of p300 histone acetylatransferase.
2006 Mar
Factors affecting the pharmacokinetic profile of MS-275, a novel histone deacetylase inhibitor, in patients with cancer.
2006 Sep
HDAC inhibitors induce apoptosis in glucocorticoid-resistant acute lymphatic leukemia cells despite a switch from the extrinsic to the intrinsic death pathway.
2007
MS-275, a potent orally available inhibitor of histone deacetylases--the development of an anticancer agent.
2007
Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents.
2007 Apr
Relationship between embryonic histonic hyperacetylation and axial skeletal defects in mouse exposed to the three HDAC inhibitors apicidin, MS-275, and sodium butyrate.
2007 Aug
Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models.
2007 Aug 1
MS-275 synergistically enhances the growth inhibitory effects of RAMBA VN/66-1 in hormone-insensitive PC-3 prostate cancer cells and tumours.
2008 Apr 8
Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells.
2008 Dec
Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG-positive prostate cancer.
2008 Dec 15
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.
2008 Jan 15
A phase I and pharmacokinetic study of the oral histone deacetylase inhibitor, MS-275, in patients with refractory solid tumors and lymphomas.
2008 Jul 15
Histone deacetylase inhibitors in lymphoma and solid malignancies.
2008 Mar
Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases.
2008 Mar 15
Evaluation of the in vitro and in vivo antitumor activity of histone deacetylase inhibitors for the therapy of retinoblastoma.
2008 May 15
MS-275, a novel histone deacetylase inhibitor with selectivity against HDAC1, induces degradation of FLT3 via inhibition of chaperone function of heat shock protein 90 in AML cells.
2008 Sep
Determination of a benzamide histone deacetylase inhibitor, MS-275, in human plasma by liquid chromatography with mass-spectrometric detection.
2009 Jan 15
Rescue of major histocompatibility-DR surface expression in retinoblastoma-defective, non-small cell lung carcinoma cells by the MS-275 histone deacetylase inhibitor.
2009 Mar
Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes.
2009 May
Three epigenetic drugs up-regulate homeobox gene Rhox5 in cancer cells through overlapping and distinct molecular mechanisms.
2009 Nov
HDAC inhibitor SNDX-275 induces apoptosis in erbB2-overexpressing breast cancer cells via down-regulation of erbB3 expression.
2009 Nov 1
Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.
2009 Sep
Antidepressant actions of histone deacetylase inhibitors.
2009 Sep 16
Anti-leukemia activity of MS-275 histone deacetylase inhibitor implicates 4-1BBL/4-1BB immunomodulatory functions.
2009 Sep 17
Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies.
2009 Sep 24
MS275 enhances cytotoxicity induced by 5-fluorouracil in the colorectal cancer cells.
2010 Feb 10
Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation.
2010 Jan 7
Patents

Sample Use Guides

Phase I trial data have shown that daily dosing of entinostat is not tolerated. Administration of the drug every 2 weeks or weekly at doses of ≤10 mg/m2 was much better tolerated than daily dosing. The recommended phase II dose for entinostat is 4 mg/ m2 once weekly (solid tumors).
Route of Administration: Oral
Entinostat (MS-275) exerts dose-dependent effects in human leukemia cells, i.e., p21(CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations (e.g., 1 uM) and a marked induction of ROS, mitochondrial damage, caspase activation, and apoptosis at higher concentrations (e.g., 5 uM).
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:58:49 GMT 2023
Edited
by admin
on Fri Dec 15 15:58:49 GMT 2023
Record UNII
1ZNY4FKK9H
Record Status Validated (UNII)
Record Version
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Name Type Language
ENTINOSTAT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
Entinostat [WHO-DD]
Common Name English
ENTINOSTAT [USAN]
Common Name English
MS-27-275
Code English
Pyridin-3-ylmethyl ({4-[(2-aminophenyl)carbamoyl]phenyl}methyl)carbamate
Systematic Name English
CARBAMIC ACID, N-((4-(((2-AMINOPHENYL)AMINO)CARBONYL)PHENYL)METHYL)-, 3- PYRIDINYLMETHYL ESTER
Common Name English
entinostat [INN]
Common Name English
MS-275-27
Code English
ENTINOSTAT [JAN]
Common Name English
SNDX-275
Code English
Classification Tree Code System Code
EU-Orphan Drug EU/3/10/732
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
NCI_THESAURUS C1946
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
Code System Code Type Description
CAS
209783-80-2
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
PUBCHEM
4261
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
DRUG BANK
DB11841
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
WIKIPEDIA
ENTINOSTAT
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
SMS_ID
100000126009
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID0041068
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
NCI_THESAURUS
C1863
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
CAS
442532-99-2
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
SUPERSEDED
INN
9016
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
USAN
TT-136
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
EVMPD
SUB33300
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
NSC
706995
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
ChEMBL
CHEMBL27759
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
FDA UNII
1ZNY4FKK9H
Created by admin on Fri Dec 15 15:58:49 GMT 2023 , Edited by admin on Fri Dec 15 15:58:49 GMT 2023
PRIMARY
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